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PloS One 2015Efavirenz, a non-nucleoside reverse-transcriptase inhibitor (NNRTI) is one of the most commonly prescribed antiretroviral drugs. The present article provides a... (Meta-Analysis)
Meta-Analysis Review
Efavirenz, a non-nucleoside reverse-transcriptase inhibitor (NNRTI) is one of the most commonly prescribed antiretroviral drugs. The present article provides a systematic overview and meta-analysis of clinical trials comparing efavirenz and other active drugs currently recommended for treatment of HIV-infected, antiretroviral-naive patients. Electronic databases (Pubmed, Embase, the Cochrane Library, Trip Database) were searched up till 23 December 2013 for randomized controlled clinical trials published as a peer-reviewed papers, and concerning efavirenz-based regimens used as initial treatment for HIV infection. Thirty-four studies were included in the systematic review, while twenty-six trials were suitable for the meta-analysis. Efavirenz was compared with drugs from four different classes: NNRTIs other than efavirenz (nevirapine or rilpivirine), integrase strand transfer inhibitors (InSTIs), ritonavir-boosted protease inhibitors (bPI) and chemokine (C-C motif) receptor 5 (CCR5) antagonists (maraviroc), all of them were added to the background regimen. Results of the current meta-analysis showed that efavirenz-based regimens were equally effective as other recommended regimens based on NNRTI, ritonavir-boosted PI or CCR5 antagonist in terms of efficacy outcomes (disease progression and/or death, plasma viral HIV RNA <50 copies/ml) while statistically significant more patients treated with InSTI achieved plasma viral load <50 copies/ml at week 48. In comparison with both InSTI-based and CCR5-based therapy, efavirenz-based treatment was associated with a higher risk of therapy discontinuation due to adverse events. However, comparisons of efevirenz-based treatment with InSTI-based and CCR5-based therapy were based on a limited number of trials, therefore, conclusions from these two comparisons must be confirmed in further reliable randomized controlled studies. Results of our meta-analysis support the present clinical guidelines for antiretroviral-naive, HIV-infected patients, in which efavirenz is one of the most preferred regimens in the analyzed population. Beneficial safety profile of InSTI-based and CCR5-based therapy over efavirenz-based treatment needs further studies.
Topics: Adult; Alkynes; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Benzoxazines; Cyclopropanes; HIV Infections; HIV Protease Inhibitors; Humans; Randomized Controlled Trials as Topic; Receptors, CCR5; Reverse Transcriptase Inhibitors; Ritonavir; Treatment Outcome
PubMed: 25933004
DOI: 10.1371/journal.pone.0124279 -
British Journal of Clinical Pharmacology Mar 2019The prevalence and incidence of atrial fibrillation/flutter (AF/AFL) in patients with human immunodeficiency virus type-1 (HIV-1) infection have been poorly...
The prevalence and incidence of atrial fibrillation/flutter (AF/AFL) in patients with human immunodeficiency virus type-1 (HIV-1) infection have been poorly investigated. We performed a systematic review using PubMed and Cochrane Database of Systematic Reviews, and screening of references, searching for clinical studies reporting on the association between HIV-1 infection and AF/AFL. We also summarized the main interactions of antiretroviral agents with antithrombotic and antiarrhythmic drugs. We found a prevalence of AF/AFL ranging from 2.0% to 5.13% in patients with HIV-1, with an incidence rate of 3.6/1000 person-years. Low CD4+ count (<200-250 cells ml ) and high viral load were predictors of AF/AFL. Regarding drugs interactions, nucleoside reverse transcriptase inhibitors, integrase inhibitor and maraviroc have the lowest interactions with oral anticoagulants. Among anticoagulants, dabigatran presents the most favourable profile. Most of antiarrhythmic drugs interact with protease inhibitors, with beta blockers and diltiazem having fewer interactions. The few studies available suggest a non-negligible prevalence of AF/AFL in patients with HIV-1 infection. Awareness of potential interactions with anticoagulation and antiarrhythmic drugs is needed to offer optimal management in this population.
Topics: Anti-Arrhythmia Agents; Anti-HIV Agents; Anticoagulants; Atrial Fibrillation; Atrial Flutter; Drug Interactions; HIV Infections; HIV-1; Humans; Incidence; Prevalence; Risk Factors; Viral Load
PubMed: 30575989
DOI: 10.1111/bcp.13837 -
HIV Medicine Mar 2012We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the overall efficacy of new antiretroviral drugs, as well as the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the overall efficacy of new antiretroviral drugs, as well as the factors associated with increased efficacy. We compared CD4 cell count increases associated with chemokine (C-C motif) receptor 5 (CCR5) inhibitors or other new drugs, using indirect comparison.
METHODS
We included RCTs published in 2003-2010 that assessed the 48-week immunological and virological efficacy of adding new antiretroviral drugs vs. placebo to optimized background therapy (OBT) in treatment-experienced subjects. These drugs included maraviroc, vicriviroc, enfuvirtide, raltegravir, etravirine, tipranavir and darunavir. We collected baseline descriptive characteristics, CD4 cell count changes and virological suppression proportions (percentage with HIV RNA <50 HIV-1 RNA copies/mL).
RESULTS
We identified 10 studies which included a total of 6401 patients. New drugs were associated with increased virological suppression (pooled odds ratio 2.97) and larger CD4 count increases (pooled nonstandardized difference 39 cells/μL) compared with placebo. OBT genotypic sensitivity scores (GSSs) were also associated with larger differences in virological suppression (P<0.001 for GSS=0,≤1 and ≤2) and CD4 cell count increase (GSS=0, P<0.001; GSS ≤1, P=0.002; GSS ≤2, P=0.015) between the two groups. CCR5 inhibitors were not associated with significant gains in CD4 cell counts (P=0.22) compared with other new drugs.
CONCLUSIONS
Our study confirmed the overall immunological and virological efficacy of new antiretroviral drugs in treatment-experienced patients, compared with placebo. The main predictive factor for efficacy was the number of fully active drugs. CCR5 inhibitors did not increase CD4 cell count to a greater extent than other new drugs.
Topics: Anti-HIV Agents; CCR5 Receptor Antagonists; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Drug Therapy, Combination; HIV Infections; HIV-1; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Viral Load
PubMed: 22107456
DOI: 10.1111/j.1468-1293.2011.00953.x -
Clinical Microbiology and Infection :... Jan 2021Several attempts have been made to test different drug-sparing strategies to reduce the drug-burden and drug-related toxicities. The objective of this meta-analysis was... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVES
Several attempts have been made to test different drug-sparing strategies to reduce the drug-burden and drug-related toxicities. The objective of this meta-analysis was to evaluate the relative risk (RR) of failure of dual therapies compared to triple therapies in HIV-naïve patients.
METHODS
We searched MEDLINE, Google Scholar and the Cochrane Library. The following criteria were used: present data from original articles comparing the two treatment regimens; published from January 2007 up to January, 2020. No language or study design restriction was applied. Subjects were HIV-positive naïve patients treated with dual or triple antiretroviral therapy (ART). A systematic review and meta-analysis was performed. Treatment failure (TF) was the primary outcome evaluated; heterogeneity was assessed using the Q statistic and I.
RESULTS
Fourteen studies were included, allowing a meta-analysis on 5205 patients. The meta-analysis performed on studies that presented data at 48 weeks showed that the RR of TF (RR > 1 favouring triple therapy) in 10 studies was 1.20 (95% confidence interval (CI): 0.91-1.59, I: 49.2%); the RR of virological failure (VF) in eight studies was 1.54 (95% CI: 0.84-2.86, I: 54%); the RR of adverse drug reaction leading to discontinuation of the regimen at 48 weeks in eight studies was 0.76 (95% CI: 0.43-1.33, I: 17.7%). In patients with less than 200 CD4+, the RR of TF in two studies without maraviroc was 2.09 (95% CI: 1.05-4.17, I: 0.0%). Regarding the studies at 96 weeks there was no difference except in rate of development of resistance, RR 1.94 (95% CI: 1.06-3.53, I: 6.2%).
CONCLUSION
Dual therapies are as effective as those with three drugs, showing no difference according to the different dual therapies, except in patients with less than 200 CD4; however, they are associated with a higher selection of resistance-associated mutations at 96 weeks of therapy.
Topics: Anti-HIV Agents; CD4-Positive T-Lymphocytes; Drug Therapy, Combination; HIV Infections; Humans; Risk; Treatment Failure
PubMed: 33031949
DOI: 10.1016/j.cmi.2020.09.048